Non-Alchohol Bioactive Essential Oil Mouth Rinses

ABSTRACT

The invention relates generally to mouth rinses for the prevention and elimination of bad breath as well as for the reduction of oral microorganisms responsible for the development of dental plaque and tooth decay. In particular, the present invention relates to a non-alcohol or reduced alcohol mouth rinses effective at preventing the above-mentioned problems.

FIELD OF THE INVENTION

The invention relates generally to mouth rinses for the prevention andelimination of bad breath as well as for the reduction of oralmicroorganisms responsible for the development of dental plaque andtooth decay. In particular, the present invention relates to anon-alcohol or reduced alcohol mouth rinses effective at preventing theabove-mentioned problems.

BACKGROUND OF THE INVENTION

Mouth rinse or mouthwash compositions have been used by people for manyyears for the prevention of bad breath and for the elimination ofbacteria and other oral microorganisms that are responsible not only forbad breath but also tooth decay, plaque and gum diseases such asgingivitis and periodontitis. To this end, antiseptic mouthwashes in thepast have been designed to clean the oral cavity, provide fresh breathand kill these pathogenic microbes.

Leading antiseptic mouth rinses have traditionally contained alcohol(i.e., ethanol) at fairly high levels, ranging from approximately 20% upto about 30% by volume, based on the total mouthwash volume (hereinafterreferred to as “% v/v”). Alcohol is used both as a vehicle and as asolvent in which the active ingredients, and additives such asastringents, fluorides, color additives, flavor oils, and the like, canbe dissolved and then dispersed into solution. Alcohol also provides apreservative role for the mouth rinse during storage and use, andenhances the flavor oil organoleptic cues.

However, the use of high levels of alcohol may sometimes be foundunacceptable by some mouthwash users. Senior citizens have alsocomplained about problems related to gargling with such mouth rinses,and chronic exposure has been found to result in a feeling of gum “burn”resulting from the high concentrations of alcohol. It has also beenreported that alcoholic mouth rinses can result in an unpleasant “drymouth” sensation.

On the other hand, reducing the levels of alcohol in these mouth rinsecompositions can have significant disadvantages. It has been found thatlower alcohol concentrations result not only in a loss in the solubilityof the actives and other ingredients in the composition, but also in anoticeable decrease in the ability of the composition to kill the oralmicroorganisms responsible for bad breath, plaque and gum disease. Thisloss in antimicrobial activity is not only due to the reduction ofalcohol as a vehicle, but also to the reduced bioavailability of thesolubilized actives.

Thymol, for example, is a well known antiseptic compound, also known asan essential oil, which is utilized for its antimicrobial activity in avariety of mouthwash or mouth rinse preparations. In particular, thymolcan be utilized in oral hygiene compositions such as mouth rinses insufficient quantities to provide desired beneficial therapeutic effects.Mouthwashes with thymol are well-known, and have been used by millionsof people for over one hundred years. They have been proven effective inkilling microbes in the oral cavity that are responsible for plaque,gingivitis and bad breath. Thymol, together with other essential oilssuch as methyl salicylate, menthol and eucalyptol, comprise the activecomponent in some antiseptic mouth rinses. These oils achieve goodefficacy although present in small amounts. Without being restricted toany specific theory, it is now believed that the efficacy and taste ofantiseptic mouth rinses may be due to the improved dispersion ordissolution of the oils and bioavailability after such dispersion ordissolution of these four active ingredients.

The above described dispersion or dissolution is also important from anaesthetic point of view since a clear mouth rinse solutions arecertainly more preferred by consumers than cloudy, turbid or otherwiseheterogeneous ones. Obviously then, there is a substantial need for thedevelopment of a reduced and/or no alcohol mouth rinses which provideimproved dispersion or dissolution of the essential oils yet maintainthe bioavailability of the essential oils for preventing bad breath,killing oral microbes and reducing or eliminating plaque.

SUMMARY OF THE INVENTION

In certain embodiments, the present invention is a reduced alcohol ornon-alcohol, antimicrobial mouth rinse composition, comprising: (a) anoil phase comprising at least one antimicrobial essential oil; (b) asolvent system comprising a polyol solvent and a sugar alcohol solvent;(c) an alkylsulfate surfactant; and (d) water.

In further embodiments, the reduced alcohol or non-alcohol,antimicrobial mouth rinse composition is a microemulsion comprisingmicelles having an aggregate size of less than about 200 nm.

In still further embodiments, the reduced alcohol or non-alcohol,antimicrobial mouth rinse composition of the present invention exhibitsa high level of antimicrobial activity as measured by an M-factorgreater than 0.5 (or about 0.5), optionally 1.0 (or about 1.0)optionally, 2.0 (or about 2.0), or optionally 3.0 (or about 3.0) where“M-factor” equals the log RLU value of water used as the negativecontrol minus the log RLU value of the mouth rinse composition beingtested. In addition, the oral mouth rinse compositions of this inventionare clear (to the unaided human eye) and aesthetically appealingproducts.

In further embodiments, the reduced alcohol or non-alcohol,antimicrobial mouth rinse composition of the present invention comprises(a) an antimicrobially effective amount of one or more antimicrobialessential oils; (b) a co-solvent of a glycol and a polyol; (c) analkylsulfate surfactant; and (d) water.

DETAILED DESCRIPTION OF THE INVENTION

The compositions of the present invention can comprise, consist of, orconsist essentially of the essential elements and limitations of theinvention described herein, as well any of the additional or optionalingredients, components, or limitations described herein. The term“comprising” (and its grammatical variations) as used herein is used inthe inclusive sense of “having” or “including” and not in the exclusivesense of “consisting only of.”

The terms “a” and “the” as used herein are understood to encompass theplural as well as the singular.

Unless otherwise indicated, all documents cited are, in relevant part,incorporated herein by reference; the citation of any document is not tobe construed as an admission that it is prior art with response to thepresent invention. Furthermore, all documents incorporated herein byreference in their entirety are only incorporated herein to the extentthat they are not inconsistent with this specification.

The reduced alcohol or non-alcohol mouthwash and mouth rinsecompositions described herein provide an antimicrobially effectiveamount of one or more antimicrobial essential oils towards oralmicroorganisms responsible for oral malodor and the build-up of plaqueand calculus and the resulting tooth and gum diseases that may follow.

The phrase “antimicrobially effective amount” means the concentration orquantity or level of the compound of the present invention that canattain a particular medical end in having toxic activity for oralmicroorganisms.

The phrase “orally acceptable” means that the carrier is suitable forapplication to the surfaces of the oral cavity or ingestion by a livingorganism including, but not limited to, mammals and humans without unduetoxicity, incompatibility, instability, allergic response, and the like.

All percentages, parts and ratios are based upon the total weight of thecomposition of the present invention, unless otherwise specified. Allsuch weights as they pertain to the listed ingredients are based on thelevel of the particular ingredient described and, therefore, do notinclude carriers or by-products that may be included in commerciallyavailable materials, unless otherwise specified.

The phrase “reduced level” of alcohol means an amount of a C₂-C₄monohydric alcohol up to 10% v/v (or about 10% v/v), optionally, up to5% v/v (or about 5% v/v), optionally, up to 1.0% v/v (or about 1.0%v/v), optionally up to 0.1% v/v (or about 0.1% v/v) by volume of thetotal composition. Optionally, the compositions of the present inventionare free of C₂-C₄ monohydric alcohols.

The term “sterile water”, as used herein, means sterile water forirrigation/injection U.S.P. The USP designation means that the sterilewater for irrigation/injection is the subject of an official monographin the current (as of the filing date of this application) USPharmacopeia.

Unless otherwise specified, the term “oil(s)” or “oily” component meansany hydrophobic, water immiscible component, including but not limitedto, essential oils (such as menthol, thymol, eucalyptol and methylsalicylate), flavor oils and hydrophobic compounds such as vitamin E,vitamin E acetate, apigenin and triclosan and mixtures of any of theabove hydrophobic, water immiscible components.

Oil Phase

The compositions of the present invention comprise an oil phasecomprising at least one oil. In certain embodiments the oil phase of thepresent invention comprises at least one antimicrobial essential oil.

Antimicrobial Essential Oils

In certain embodiments, the enhanced antimicrobial efficacy of thenon-alcohol mouth rinse compositions herein is attributed to thepresence of minor amounts of one or more antimicrobial or bioactiveessential oils (i.e. thymol, eucalyptol, menthol and methyl salicylate).

Thymol, [(CH₃)₂CHC₆H₃(CH₃)OH, also known as isopropyl-m-cresol], is onlyslightly soluble in water but is soluble in alcohol, and its presence isone of the reasons alcohol was necessary in the well-established, highalcohol commercial mouth rinses. Methyl salicylate, [C₆H₄OHCOOCH₃, alsoknown as wintergreen oil], additionally provides flavoring to thetogether with its antimicrobial function. Eucalyptol (C₁₀H₁₈O, alsoknown as cineol) is a terpene ether and provides a cooling, spicy taste.Eucalyptol may be used in place of thymol in certain formulations in thesame amount if desired. Menthol (CH₃C₆H₉(C₃H₇)OH), also known ashexahydrothymol) is also only slightly soluble in alcohol, and is fairlyvolatile. Menthol, in addition to any antiseptic properties, provides acooling, tingling sensation.

In certain embodiments, the essential oils are used in amounts effectiveto provide antimicrobial activity in the oral cavity. In specificembodiments, the total amount of essential oils present in the disclosedcompositions can be from 0.001% (or about 0.001%) to 0.35% (or about0.35%) w/v, or optionally from 0.16% (or about 0.16%) to 0.28% (or about0.28%) w/v of the composition.

In some embodiments, the compositions of the present invention containthymol and additionally eucalyptol, menthol, or methyl salicylate, ormixtures thereof. Optionally, the composition contains all four of theseessential oils.

In certain embodiments, thymol is employed in amounts of from 0.001% (orabout 0.001%) to 0.25% (or about 0.25%) w/v, or optionally from 0.04%(or about 0.04%) to 0.07% (or about 0.07%) w/v of the composition. Incertain embodiments, eucalyptol may be employed in amounts of from0.001% (or about 0.001%) to 0.11% (or about 0.11%) w/v, or optionallyfrom 0.085% (or about 0.085%) to 0.10% (or about 0.10%) w/v of thecomposition. In certain embodiments, menthol is employed in amounts offrom 0.001% (or about 0.001%) to 0.25% (or about 0.25%) w/v, oroptionally from 0.035% (or about 0.035%) to 0.05% (or about 0.05%) w/vof the composition. In certain embodiments, methyl salicylate isemployed in amounts of from 0.001% (or about 0.001%) to 0.08% (or about0.08%) w/v, or optionally from 0.04% (or about 0.04%) to 0.07% (or about0.07%) w/v of the composition.

In some embodiments, the carrier for the essential oils (the activeingredients) is typically a water-alcohol mixture, generallywater-ethanol. In the past, some antiseptic oral mouth rinsecompositions, required ethanol levels of up to about 27% v/v. These highlevels were necessary to assist the actives in providing the necessaryantimicrobial functionality as well as providing a clear, aestheticallyattractive liquid medium. Merely reducing the alcohol levels, withoutthe addition of other formulation components, results in a cloudy, lessefficacious product.

Without being bound to any theory, it is believed that in these highalcohol level oral compositions, the alcohol solubilizes theantimicrobial essential oils and in so doing acts by an activeenhancement mechanism. The antimicrobial essential oils are more readilydispersed throughout the solution and remain free or unbound to attackpathogenic microbes throughout the oral cavity. Reducing the alcohollevels was believed to adversely affect this enhancement mechanism. Inaccordance with the present invention, however, it was surprisingly andunexpectedly found that the level of alcohol can be reduced oreliminated without sacrificing antimicrobial efficacy or clarity if themouth rinse composition contains a solvent system and alkyl sulfatesurfactant as taught herein.

In certain embodiments, the total amount of oil phase present in thedisclosed compositions of the present invention should not exceed 1.35%w/v (or about 1.35% w/v) of the mouth rinse composition. Optionally, thetotal oil phase, can be present in an amount of from 0.04% (or about0.04%) to 1.35% (or about 1.35%) w/v, or optionally from 0.10% (or about0.10%) to 0.4% (or about 0.4%) w/v of the mouth rinse composition.

Solvent System

In certain embodiments, the mouth rinse compositions of the presentinvention also include a solvent system comprising at least one polyolsolvent and at least one sugar alcohol.

Polyol Solvent

Polyol or polyhydric alcohol solvents suitable for use in the solventsystem of the present invention includes polyhydric alkanes (such aspropylene glycol, glycerin, butylene glycol, hexylene glycol,1,3-propanediol); polyhydric alkane esters (dipropylene glycol,ethoxydiglycol); polyalkene glycols (such as polyethylene glycol,polypropylene glycol) and mixtures thereof. In certain embodiments, thepolyol solvent can be present in an amount of from 1.0% (or about 1.0%)to 30.0% (or about 30.0%) w/v, or optionally from 5.0% (or about 5.0%)to 15.0% (or about 15.0%) w/v of the composition.

Sugar Alcohol Solvent

The sugar alcohol solvent(s) may be selected from thosemulti-hydroxy-functional compounds that are conventionally used in oraland ingestible products. In certain embodiments, the sugar alcohol (s)should be non-metabolized and non-fermentable sugar alcohol (s). Inspecific embodiments, the sugar alcohols include, but are not limited toxylitol, sorbitol, mannitol, maltitol, inositol, allitol, altritol,dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol,erythritol and mixtures thereof. Optionally, the sugar alcohol isselected from the group consisting of sorbitol and xylitol or mixturesthereof. Optionally, the sugar alcohol is sorbitol.

In certain embodiments, the total amount of sugar alcohol (s) which areadded to effectively aid in the dispersion or dissolution of the activeingredients should not exceed 17% w/v (or about 17% w/v) of thecomposition. Optionally, total amount of sugar alcohol should not exceed10% w/v (or about 10% w/v) of the composition. The sugar alcohol can bein an amount of from 1.0% (or about 1.0%) to 17.0% (or about 17.0%) w/v,or optionally from 5.0% (or about 5.0%) to 15.0% (or about 15.0%) w/v ofthe composition.

In certain embodiments, the total amount of the solvent system which isadded to effectively aid in the dissolution or dispersion of the activeingredients should not exceed 47% w/v (or about 47% w/v) of thecomposition. Optionally, total amount of solvent system should notexceed 20% w/v (or about 20% w/v) of the composition. The solvent systemcan be in an amount of from 2% (or about 2%) to 47% (or about 47%) w/v,or optionally from 10% (or about 10%) to 20% (or about 20%) w/v of thecomposition.

In certain embodiments, the ratio of the sugar alcohol to the polyolsolvent in the composition should be from 10:1 (or about 10:10) to 1:10(or about 1:10), optionally from 5:1 (or about 5:1) to 1:5 (or about1:5), optionally 1:1 (or about 1:1) by weight.

Alkyl Sulfate Surfactant

The mouth rinse compositions of the present invention also contain atleast one alkyl sulfate surfactant. In certain embodiments, suitablealkyl sulfate surfactants include, but are not limited to sulfated C₈ toC₁₈, optionally sulfated C₁₀ to C₁₆ even numbered carbon chain lengthalcohols neutralized with a suitable basic salt such as sodium carbonateor sodium hydroxide and mixtures thereof such that the alkyl sulfatesurfactant has an even numbered C₈ to C₁₈, optionally C₁₀ to C₁₆, chainlength. In certain embodiments, the alkyl sulfate is selected from thegroup consisting of sodium lauryl sulfate, hexadecyl sulfate andmixtures thereof. In certain embodiments, commercially availablemixtures of alkyl sulfates are used. A typical percentage breakdown ofalkyl sulfates by alkyl chain length in commercially available sodiumlauryl sulfate (SLS) is as follows:

Component Alkyl Chain Percentage Length in SLS C₁₂ >60% C₁₄   20%-35%C₁₆ <10% C₁₀  <1% C₁₈  <1%

Suitable commercially available mixtures include Stepanol WA-100 NF USP,(Stepan, Northfield, Ill.), Texapon K12 G PH, (Texapon, Cognis, Germany)and mixtures thereof.

In certain embodiments, where the amount of the alkyl sulfate surfactantadded to the composition can be from 0.05% (or about 0.05%) to 2.0% (orabout 2.0%) w/v, or optionally from 0.1% (or about 0.1%) to 0.5% (orabout 0.5%) w/v of the composition.

Additional surfactants may be added with the alkyl sulfate surfactant toaid in solubilization of the essential oils provided such surfactants donot affect the bioavailability of the essential oils. Suitable examplesinclude additional anionic surfactants, nonionic surfactants, amphotericsurfactants and mixtures thereof. However, in certain embodiments, thetotal surfactant concentration (including the alkyl sulfate surfactantalone or in combination with other surfactants) of the mouth rinses ofthe present invention should not exceed or should be less than 2% (orabout 2%), optionally, the total surfactant concentration should notexceed or should be less than 1.5% (or about 1.5%), optionally, thetotal surfactant concentration should not exceed or should be less than1.0% (or about 1.0%), optionally, the total surfactant concentrationshould not exceed or should be less than 0.5% (or about 0.5%) by weightof the composition.

Anionic surfactants useful herein include, but are not limited to,sarcosine type surfactants or sarcosinates; taurates such as sodiummethyl cocoyl taurate; sodium lauryl sulfoacetate; sodium lauroylisethionate; sodium laureth carboxylate; sodium dodecyl benzenesulfonateand mixtures thereof. Many suitable anionic surfactants are disclosed inU.S. Pat. No. 3,959,458, to Agricola, et al., herein incorporated byreference in its entirety.

Nonionic surfactants which can be used in the compositions of thepresent invention include, but are not limited to, compounds produced bythe condensation of alkylene oxide groups (hydrophilic in nature) withan organic hydrophobic compound which may be aliphatic or alkyl-aromaticin nature. Examples of suitable nonionic surfactants include, but arenot limited to, alkyl polyglucosides; ethoxylated hydrogenated castoroils available commercially for example under the trade name CRODURET(Croda Inc., Edison, N.J.), and/or; fatty alcohol ethoxylates;polyethylene oxide condensates of alkyl phenols; products derived fromthe condensation of ethylene oxide with the reaction product ofpropylene oxide and ethylene diamine; ethylene oxide condensates ofaliphatic alcohols; long chain tertiary amine oxides; long chaintertiary phosphine oxides; long chain dialkyl sulfoxides; and mixturesthereof.

The amphoteric surfactants useful in the present invention include, butare not limited to, derivatives of aliphatic secondary and tertiaryamines in which the aliphatic radical can be a straight chain orbranched and wherein one of the aliphatic substituents contains fromabout 8 to about 18 carbon atoms and one contains an anionicwater-solubilizing group, e.g., carboxylate, sulfonate, sulfate,phosphate, or phosphonate. Examples of suitable amphoteric surfactantsinclude, but are not limited alkylimino-diproprionates,alkylamphoglycinates (mono or di), alkylamphoproprionates (mono or di),alkylamphoacetates (mono or di), N-alkyl β-aminoproprionic acids,alkylpolyamino carboxylates, phosphorylated imidazolines, alkylbetaines, alkylamido betaines, alkylamidopropyl betaines, alkylsultaines, alkylamido sultaines, and mixtures thereof. In certainembodiments, the amphoteric surfactant is selected from the groupconsisting of alkylamidopropyl betaines, amphoacetates such as sodiumlauroamphoacetate and mixtures thereof. Mixtures of any of the abovementioned surfactants can also be employed. A more detailed discussionof anionic, nonionic and amphoteric surfactants can be found in U.S.Pat. Nos. 7,087,650 to Lennon; 7,084,104 to Martin et al.; 5,190,747 toSekiguchi et al.; and 4,051,234, Gieske, et al., each of which patentsare herein incorporated by reference in their entirety.

In certain embodiments, the additional surfactant to be added the mouthrinses of the present invention with the alkyl sulfate surfactant isselected from the group consisting of taurates. Optionally, theadditional surfactant is selected from the group consisting of sodiummethyl lauryl taurate, sodium methyl oleoyl taurate, sodium methylcocoyl taurate and mixtures thereof. In certain embodiments, theadditional surfactant is sodium methyl cocoyl taurate.

In certain embodiments, the ratio of the solvent system to the totalamount of surfactant in the composition should be from 360:1 (or about360:1) to 10:1 (or about 10:1), optionally from 100:1 (or about 100:1)to 20:1 (or about 20:1) by weight.

In further embodiments, the ratio of the oil phase to the solvent systemto the total amount of surfactant (or, the total surfactantconcentration including the alkyl sulfate surfactant) by weight is1:200:1.5 (or about 1:200:1.5) or, optionally, 1:60:1.5 (or about1:60:1.5) by weight.

Aqueous Phase

An aqueous phase comprising water is added to the oil phase of thepresent compositions to form oil-in-water or water-in-oil dispersions,micro emulsions or emulsions.

In certain embodiments, the aqueous phase comprises from about 60% toabout 95%, or optionally from about 75% to about 93%, by weight of thecomposition.

Alternatively, the mouth rinse compositions of the present invention maybe formulated in a dry powder, chewing gum, semi-solid, solid or liquidconcentrate form. In such embodiments, for example, water is added toq.s. as necessary in the case of liquid concentrates or powderedformulations, or water may be removed using standard evaporationprocedures known in the art to produce a composition in dry powder form.Evaporated, or freeze dried forms are advantageous for storage andshipping.

Micelle Size

The mouth rinse compositions of the present invention comprise colloidalaggregates of amphipathic molecules called micelles. In certainembodiments, the micelles of the present invention have an aggregatesize of less than 200 nm (or about 200 nm), optionally 100 nm (or about100 nm), optionally 50 nm (or about 50 nm), or optionally 10 nm (orabout 10).

Optional Ingredients Insoluble Particulates

In certain embodiments, the oral care compositions of the presentinvention optionally comprise a safe and effective amount of a waterinsoluble particulate. The water insoluble particulate can be anabrasive particle (such as a dentally acceptable abrasive) ornon-abrasive particulate.

In certain embodiments, dentally acceptable abrasives include, but arenot limited to, water insoluble calcium salts such as calcium carbonate,and various calcium phosphates, alumina, silica, synthetic resins andmixtures thereof. Suitable dentally acceptable abrasives may generallybe defined as those having a radioactive dentine abrasion value (RDA) offrom about 30 to about 250 at the concentrations used in thecompositions of the present invention. In certain embodiments, abrasivesare non-crystalline, hydrated, silica abrasives, particularly in theform of precipitated silica or milled silica gels availablecommercially, for example, under the trade names ZEODENT (J. M. HuberCorporation, Edison, N.J.), and SYLODENT (W.R. Grace & Co., New York,N.Y.), respectively. In certain embodiments, the compositions accordingto the present invention comprise from about 1% to about 20%, or,optionally, from about 5% to about 10% by weight of the abrasive.

Alternatively, the insoluble particulate is a non-abrasive particulatewhich is visible to the unaided eye and stable in the compositions ofthe present invention.

The non-abrasive particulate can be of any size, shape, or color,according to the desired characteristic of the product. The non-abrasiveparticulates will typically have the shape of a small round orsubstantially round ball or sphere, however, platelet or rod-shapedconfigurations are also contemplated herein. Generally, a non-abrasiveparticulate has an average diameter of from about 50 μm to about 5000μm, optionally from about 100 μm to about 3000 μm, or optionally fromabout 300 μm to about 1000 μm. By the terms “stable” and/or “stability”,it is meant that the abrasive or non-abrasive particulates are notdisintegrated, agglomerated, or separated under normal shelf conditions.In certain embodiments, the terms “stable” and/or “stability” furthermean that the compositions of present invention contain no visible orminimally visible (to the unaided eye) signs of sedimentation of theinsoluble particulates after 8 weeks, optionally 26 weeks, optionally 52weeks, at room temperature.

The non-abrasive particulates herein are typically incorporated in thepresent compositions at levels of from about 0.01% to about 25%,optionally, from about 0.01% to about 5%, or optionally, from about0.05% to about 3%, by weight of the composition.

The non-abrasive particulate herein will typically comprise a structuralmaterial and/or, optionally, an encompassed material.

The structural material provides a certain strength to the non-abrasiveparticulates so that they retain their distinctively detectablestructure in the compositions of the present invention under normalshelf conditions. In one embodiment, the structural material further canbe broken and disintegrated with very little shear on the teeth, tongueor oral mucosa upon use.

The non-abrasive particulates can be solid or liquid, filled orun-filled, as long as they are stable in the compositions of the presentinvention. The structural material used for making the non-abrasiveparticulates varies depending on the compatibility with othercomponents, as well as material, if any, to be encompassed in thenon-abrasive particulates. Exemplary materials for making thenon-abrasive particulates herein include: polysaccharide and saccharidederivatives such as crystalline cellulose, cellulose acetate, celluloseacetate butyrate, cellulose acetate phthalate, cellulose nitrate,ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose,hydroxypropylmethylcellulose phthalate, methyl cellulose, sodiumcarboxymethylcellulose, gum acacia (gum arabic), agar, agarose,maltodextrin, sodium alginate, calcium alginate, dextran, starch,galactose, glucosamine, cyclodextrin, chitin, amylose, amylopectin,glycogen, laminaran, lichenan, curdlan, inulin, levan, pectin, mannan,xylan, alginic acid, arabic acid, glucommannan, agarose, agaropectin,prophyran, carrageenen, fucoidan, glycosaminoglycan, hyaluronic acid,chondroitin, peptidoglycan, lipopolysaccharide, guar gum, starch, andstarch derivatives; oligosaccharides such as sucrose, lactose, maltose,uronic acid, muramic acid, cellobiose, isomaltose, planteose,melezitose, gentianose, maltotriose, stachyose, glucoside andpolyglucoside; monosaccharides such as glucose, fructose, and mannose;synthetic polymers such as acrylic polymers and copolymers includingpolyacrylamide, poly(alkyl cyanoacrylate), and poly(ethylene-vinylacetate), and carboxyvinyl polymer, polyamide, poly(methyl vinylether-maleic anhydride), poly(adipyl-L-lysine), polycarbonate,polyterephthalamide, polyvinyl acetate phthalate,poly(terephthaloyl-L-lysine), polyarylsulfone, poly(methylmethacrylate),poly(ε-caprolactone), polyvinylpyrrolidone, polydimethylsiloxane,polyoxyethylene, polyester, polyglycolic acid, polylactic acid,polyglutamic acid, polylysine, polystyrene, poly(styrene-acrylonitrile),polyimide, and poly(vinyl alcohol); and other material such as fat,fatty acid, fatty alcohol, milk solids, molasses, gelatin, gluten,albumin, shellac, caseinate, bees wax, carnauba wax, spermaceti wax,hydrogenated tallow, glycerol monopalmitate, glycerol dipalmitate,hydrogenated castor oil, glycerol monostearate, glycerol distearate,glycerol tristearate, 12-hydroxystearyl alcohol, protein, and proteinderivatives; and mixtures thereof. Components herein may be described inother sections as useful components for the present composition. Incertain embodiments, the components as described in this section formthe structure of the non-abrasive particulates so as to not besubstantially dissolved or dispersed from the particulates and into thecompositions of the present invention under normal shelf conditions.

In other embodiments, the structural material herein comprisescomponents selected from the group consisting of polysaccharides andtheir derivatives, saccharides and their derivatives, oligosaccharides,monosaccharides, and mixtures thereof, or optionally, comprisescomponents are having various degrees of water solubility. In someembodiments, the structural material comprises lactose, cellulose, andhydroxypropyl methylcellulose.

Suitable non-abrasive particulates also include organogel particles asdescribed in detail in U.S. Pat. No. 6,797,683, herein corporate byreference in its entirety. Non-abrasive particulates that are organogelparticles typically comprise a structural material selected from waxes(e.g., beeswax, paraffin, water-insoluble wax, carbon-based wax,silicone wax, microcrystalline wax, etc.), triglycerides, acidtriglycerides, polymers, fluoroalkyl (meth)acrylate polymers andcopolymers, acrylate polymers, ethylene/acrylate copolymers,polyethylene, polypropylene polymers and copolymers, fatty acids, fattyalcohols, fatty acid esters, fatty acid ethers, fatty acid amides,alkylene polyhydric alcohols, fatty acid amide of an alkanolamine,glyceryl monostearate, (aryl-substituted) sugars, dibenzyl sorbitol (ormannitoal, rabbitol, etc.), condensates and precondensates of lowermonohydric alcohols, trihydroic alcohols, lower polyglycols,propylene/ethylene polycondensates, and the like. Optionally, structuralmaterial for non-abrasive particulates that are organogel particlesinclude beeswax, carnauba wax, low molecular weight ethylenehomopolymers (e.g. Polywax 500, Polywax 1000, or Polywax 2000polyethylene materials available from Baker Petrolite Corp.), orparaffin wax.

The non-abrasive particulates herein may encompass, contain, or befilled with an encompassed material. Such encompassed material can bewater soluble or water insoluble. Suitable encompassed materials includebenefit agents as described herein such as: oral care actives, vitamins,pigments, dyes, antimicrobial agents, chelating agents, opticalbrighteners, flavors, perfumes, humectants, minerals, and mixturesthereof. The encompassed materials herein are substantially retainedwithin the non-abrasive particulates, and are substantially notdissolved from the particulates and into the compositions of the presentcomposition under normal shelf conditions.

Particularly useful commercially available non-abrasive particulatesherein are those with tradenames Unisphere and Unicerin available fromInduchem AG (Switzerland), and Confetti Dermal Essentials available fromUnited-Guardian Inc. (NY, USA). Unisphere and Unicerin particles aremade of microcrystalline cellulose, hydroxypropyl cellulose, lactose,vitamins, pigments, and proteins. Upon use, the Unisphere and Unicerinparticles can be disintegrated with very little shear and withpractically no resistance, and readily disperse in the compositions ofthe present invention.

Suitable non-abrasive particulates for incorporation in the presentcompositions are described in detail in U.S. Pat. No. 6,797,683(organogel particles); U.S. Pat. No. 6,045,813 (rupturable beads); U.S.Pat. Publ. 2004/0047822 A1 (visible capsules); and U.S. Pat. No.6,106,815 (capsulated or particulated oily substances), each of whichpatent documents are herein incorporated by reference in their entirety.

In certain embodiments, the abrasive and/or nonabrasive particles have adensity different or, optionally, substantially different from thecarrier in which these particles are formulated.

Flavors or Flavorants

In certain embodiments, flavors or flavorants may also be added tofurther modify or magnify the taste of the mouth rinse, or reduce ormask the sharp “bite” or “burn” of ingredients such as thymol. Suitableflavors include, but are not limited to, oil of anise, anethole, benzylalcohol, spearmint oil, citrus oils, vanillin and the like may beincorporated. In these embodiments, the amount of flavor oil added tothe composition can be from 0.001% (or about 0.001%) to 1.0% (or about1.0%) w/v, or optionally from 0.1% (or about 0.10%) to 0.30% (or about0.30%) w/v of the composition.

The particular flavors or flavorants, and other taste-improvingingredients, employed will vary depending upon the particular taste andfeel desired. Those skilled in the art can select and customize thesetypes of ingredients to provide the desired results.

Buffers

In certain embodiments, additional conventional components may be addedas in mouthwashes and mouth rinses of the prior art. Whereas somealcohol containing mouth rinses have a pH of about 7.0, reduction of thealcohol level may require the addition of acidic preservatives, such assorbic acid or benzoic acid, which reduce pH levels. Buffer systems arethen necessary to control the pH of the composition at optimal levels.This is generally accomplished through the addition of a weak acid andits salt or a weak base and its salt. In some embodiments, usefulsystems have been found to be sodium benzoate and benzoic acid inamounts of from 0.01% (or about 0.01% w/v) to 1.0% w/v (or about 1.0%w/v) of the composition, and sodium citrate and citric acid in amountsof from 0.001% (or about 0.001% w/v) to 1.0% w/v (or about 1.0% w/v) ofthe composition, phosphoric acid and sodium/potassium phosphate ofamounts from 0.01% (or about 0.01%) to 1.0% (or about 1.0%) by weight ofthe composition. In certain embodiments, the buffers are incorporated inamounts that maintain the pH at levels of from 3.0 (or about 3.0) to 8.0(or about 8.0), optionally from 3.5 (or about 3.5) to 6.5 (or about6.5), optionally from 3.5 (or about 3.5) to 5.0 (or about 5.0). Withoutbeing limited by any theory, it is believed that these pH levels providethe essential oils with an environment that also maximizes theirantimicrobial activity and promotes stability.

Fluoride Releasing Compounds

In certain embodiments, fluoride providing compounds may be present inthe mouth rinse compositions of this invention. These compounds may beslightly water soluble or may be fully water soluble and arecharacterized by their ability to release fluoride ions or fluoridecontaining ions in water. Typical fluoride providing compounds areinorganic fluoride salts such as soluble alkali metal, alkaline earthmetal, and heavy metal salts, for example, sodium fluoride, potassiumfluoride, ammonium fluoride, cupric fluoride, zinc fluoride, stannicfluoride, stannous fluoride, barium fluoride, sodium hexafluorosilicate,ammonium hexafluorosilicate, sodium fluorozirconate, sodiummonofluorophosphate, aluminum mono- and difluorophosphate andfluorinated sodium calcium pyrophosphate. Amine fluorides, such asN′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluorideand 9-octadecenylamine-hydrofluoride), may also be used.

In certain embodiments, the fluoride providing compound is generallypresent in an amount sufficient to release up to 0.15% (or about 0.15%),optionally 0.001% (or about 0.001%) to 0.1% (or about 0.1%), optionallyfrom 0.001% (or about 0.001%) to 0.05% (or about 0.05%) fluoride byweight of the composition.

Zinc Salts

In certain embodiments, zinc salts such as zinc chloride, zinc acetateor zinc citrate may be added as an astringent for an “antisepticcleaning” feeling, as a breath protection enhancer or as anticalculusagent in an amount of from 0.0025% w/v (or about 0.0025% w/v) to 0.1%w/v (or about 0.1% w/v) of the composition.

Sensitivity Reducing Agents

In certain embodiments, sensitivity reducing agents, namely potassiumsalts of nitrate and oxalate in an amount from 0.1% (or about 0.1%) to5.0% (or about 5.0%) w/v of the composition may be incorporated into thepresent invention. Other potassium releasing compounds are feasible(e.g. KCl). High concentrations of calcium phosphates may also providesome added sensitivity relief. These agents are believed to work byeither forming an occlusive surface mineral deposit on the tooth surfaceor through providing potassium to the nerves within the teeth todepolarize the nerves. A more detailed discussion of suitablesensitivity reducing can be found in US 20060013778 to Hodosh and U.S.Pat. No. 6,416,745 to Markowitz et al., both of which are hereinincorporated by reference in their entirety.

Anticalculus Agents

In certain embodiments, compounds with anti-calculus benefits (e.g.polyphosphates, phosphonates, various carboxylates, polyaspartic acid,inositol phosphate etc.) may be incorporated into the present invention.Also useful as an anticalculus agent are the anionic polymericpolycarboxylates. Such materials are well known in the art, beingemployed in the form of their free acids or partially or preferablyfully neutralized water soluble alkali metal (e.g. potassium andpreferably sodium) or ammonium salts. Preferred are 1:4 to 4:1 by weightcopolymers of maleic anhydride or acid with another polymerizableethylenically unsaturated monomer, preferably methyl vinyl ether(methoxyethylene) having a molecular weight (M.W.) of about 30,000 toabout 1,000,000. These copolymers are available for example as GantrezAN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation.

Additional Ingredients

Although the mouth rinse compositions of the present invention may beformulated to be substantially clear and/or colorless to the unaidedeye, acceptably approved food dyes are preferably used to provide apleasing color to the compositions of the invention. These may beselected from, but not limited to, the long list of acceptable fooddyes. Suitable dyes for this purpose include FD&C yellow #5, FD&C yellow#10, FD&C blue #1 and FD&C green #3. These are added in conventionalamounts, typically in individual amounts of from 0.00001% w/v (or about0.00001% w/v) to 0.0008% w/v (or about 0.0008% w/v), optionally from0.00035% w/v (or about 0.00035% w/v) to 0.0005% w/v (or about 0.0005%w/v) of the composition.

Other conventional ingredients may be used in the mouth rinsecompositions of this invention, including those known and used in theart. Examples of such ingredients include thickeners, suspending agentsand softeners. Thickeners and suspending agents useful in thecompositions of the present invention can be found in U.S. Pat. No.5,328,682 to Pullen et al., herein incorporated by reference in itsentirety. In certain embodiments, these are incorporated in amounts offrom 0.1% w/v (about 0.1% w/v) to 0.6% w/v (or about 0.6% w/v),optionally 0.5% w/v (or about 0.5% w/v) of the composition.

A more detailed description of useful oral care actives and/or inactiveingredients and further examples thereof can be found in U.S. Pat. Nos.6,682,722 to Majeti et al. and 6,121,315 to Nair et al., each of whichare herein incorporated by reference in its entirety.

In certain embodiments, the compositions of the present invention arefree of or essentially free of bioavailability affecting compounds. Asused herein, “bioavailability affecting compound”, means compounds thatnegatively affect the bioavailability of any incorporated essential oilssuch as by binding the essential oils or otherwise inactivating theessential oils. “Essentially free” as used with respect tobioavailability affecting compounds is defined as formulations havingless than 5% (or about 5%), optionally, 3% (or about 3%), optionally, 1%(or about 1%), or optionally 0.1, or optionally, 0.01% (or about 0.01%),by weight (w/v) of the total composition of a bioavailability affectingcompound. In certain embodiments, the bioavailability affecting compoundcan include, but is not limited to, polyethylene oxide/polypropyleneoxide block copolymers such as poloxamers; cyclodextrins; polysorbatessuch as Tweens; and mixtures thereof.

Methods of Practicing the Present Invention

The invention illustratively disclosed herein may be practiced in theabsence of any component, ingredient, or step which is not specificallydisclosed herein.

In certain embodiments, the compositions of the present invention areapplied to teeth and/or soft surfaces of the oral cavity for at leasttwo consecutive applications, optionally, at least (or greater than) 3(or about 3) or optionally, at least (or greater than) 5 (or about 5)consecutive applications.

When applied to teeth and/or soft surfaces of the oral cavity, incertain embodiments, the composition is allowed to remain in contactwith the teeth and/or soft surfaces of the oral cavity for at least (orgreater than) 10 (or about 10) seconds, optionally 20 (or about 20)seconds, optionally 30 (or about 30) seconds, optionally 50 (or about50) seconds, or optionally 60 (or about 60) seconds.

Various embodiments of the invention have been set forth above. Eachembodiment is provided by way of explanation of the invention, notlimitation of the invention. In fact, it will be apparent to thoseskilled in the art that various modifications and variations can be madein the present invention without departing from the scope or spirit ofthe invention. For instance, features illustrated or described as partof one embodiment, can be used on another embodiment to yield a stillfurther embodiment. Thus, it is intended that the present inventioncover such modifications and variations as come within the scope of theappended claims and their equivalents.

EXAMPLES

The following examples are illustrative only and should not be construedas limiting the invention in any way. Those skilled in the art willappreciate that variations are possible which are within the spirit andscope of the appended claims.

Example 1 Solubilization of Essential Oils with Cyclodextrins(Comparative Example)

Four formulations were prepared and tested for mixed-species biofilmkill analysis using a flow cell model. A 48-hour salivary biofilm wasgrown on a polystyrene peg plate (96 pegs, N=8 per test group). The pegswere subsequently treated for thirty seconds with each of the fourformulations, as well as positive and negative controls. Treatmentsoccurred twice daily for a total of five treatments. The positivecontrol was a commercially available essential oil mouth rinse. Thenegative control was sterile water.

After treatment, viable bacteria remaining on the substrate were removedby sonication using a Misonix XL-2000 Ultrasonic processor (Qsonica,LLC, Newtown, Conn.). Using a Celsis Rapid Detection RapiScreen kit(Celsis International PLC, Chicago), the bacteria was lysed with CelsisLuminex and then the adenosine triphosphate (ATP) released from thelysed bacteria was measured using the bioluminescence marker CelsisLuminATE. Data was reported in log RLU (relative light units) wheredecreasing log RLUs indicates fewer viable bacteria remaining on thesubstrate and in M-factor units where M-factor is the difference betweenthe log RLU values of the compound tested and the negative control.

The four formulations, as well as results of the mixed-species biofilmkill tests, are shown on Table 1. Final formulations were adjusted to pH4.2 with 0.1M NaOH or 0.1M HCl if necessary.

TABLE 1 Formulations Positive Negative 1A 1B 1C 1D Control ControlIngredients (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) PurifiedWater USP QS QS QS QS QS 100 Hydroxypropyl Cyclodextrin 2.00 2.00 0.002.00 — — Poloxamer 407 — — — — 0.25 — Thymol 0.06 0.06 — — 0.0636 —Menthol 0.04 0.04 — — 0.0420 — Eucalyptol 0.09 0.09 — — 0.0922 — MethylSalicylate 0.06 0.06 — — 0.060 — Glycerin 5.00 5.00 5.00 5.00 — —Soribitol (70% solution) 5.00 5.00 5.00 5.00 20.0 — Benzoic Acid — — — —0.12 — Citric Acid 0.10 0.10 0.10 0.10 — — NaOH 0.25 0.25 0.25 0.25 — —Ethanol-200 — 20.00 20.00 — 21.6 — proof (v/v) Flavor — — — — 0.085 —Sweetener — — — — 0.117 — Color — — — — 0.0005 — Total 100.00 100.00100.00 100.00 100.00 — log RLU 7.50 8.00 8.09 7.94 5.67 7.54 M-factor0.04 −0.46 −0.55 −0.40 1.87 0

The M-factors for formulations 1A through 1D were less than 0.1. Thisdata indicates that the essential oils, though solubilized in thecyclodextrin formulas, are not sufficiently bio-available to killbacterial species in a biofilm. The commercially available alcoholcontaining essential oil mouth rinse provided a relatively high M-factorwith M-factor equal to 1.87.

Example 2 Various Surfactants

Seven propylene-glycol based mouth rinse formulations were preparedusing various surfactants that are approved for use in oral careproducts and tested using an in-vitro single species S. mutans biofilmmodel. A 22-hour S. mutans biofilm was grown (N=32) and exposed to theformulations as well as positive and negative controls for 30 seconds.Sterile water was used as the negative control. After treatment thebiofilm was neutralized and rinsed. The biofilm was harvested viasonication using a Misonix XL-2000 Ultrasonic processor (Qsonica, LLC,Newtown, Conn.). Using a Celsis Rapid Detection RapiScreen kit (CelsisInternational PLC, Chicago). The bacteria was lysed with Celsis Luminexand the ATP from the bacteria was measured using the bioluminescencemarker Celsis LuminATE. Decreasing log RLUs (relative light units)indicates fewer bacteria alive after treatment.

The seven formulations, as well as results of the S. mutans biofilm killtests, in log RLU and M-Factor units, are shown on Table 2. Finalformulations were adjusted to pH 4.2 with 0.1M NaOH or 0.1M HCl ifnecessary. A typical M-factor for a commercially available alcoholcontaining essential oil mouth rinse is about 2.1 (log RLU of 5.8) inthis model.

TABLE 2 Formulations 2A 2B 2C 2D 2E 2F 2G Negative (% (% (% (% (% (% (%Control Ingredients w/w) w/w) w/w) w/w) w/w) w/w) w/w) (% w/w) Propylene10.0 10.0 10.0 10.0 10.0 10.0 10.0 100 glycol Benzoic 0.30 0.30 0.300.30 0.30 0.30 0.30 — Acid Menthol 0.042 0.042 0.042 0.042 0.042 0.0420.042 — Methyl 0.060 0.060 0.060 0.060 0.060 0.060 0.060 — salicylateThymol 0.064 0.064 0.064 0.064 0.064 0.064 0.064 — Eucalyptol 0.0920.092 0.092 0.092 0.092 0.092 0.092 — Tween 20 — 2.00 — — — — — — SodiumLauryl 0.30 — 1.00 — — 0.30 0.15 — Sulfate Cocamidopr — — — 1.00 — — — —opyl betaine Hexadecyl sulfate — — — — 0.30 — 0.15 — Sorbitol — — — — —10.00 — — (70% solution) Sodium 0.30 0.30 0.30 0.30 0.30 0.30 0.30 —Benzoate Purified QS QS QS QS QS QS QS — Water USP TOTAL 100.0 100.0100.0 100.0 100.0 100.0 100.0 — log RLU 5.63 8.02 5.30 7.73 6.50 4.524.22 7.90 M-factor 2.27 −0.12 2.60 0.17 1.40 3.38 3.68 0

Table 2 shows biocidal activity ranges significantly depending on theidentity of the surfactant, with alkyl sulfates and alkyl sulfatecombinations displaying the highest activity (M-factor greater than2.0.) Additionally, it was observed that sorbitol increases bioactivityas well, as otherwise identical formulation 2A without sorbitol providedM-factor of 2.27 while formulation 2F with sorbital provided a muchgreater M-factor of 3.68.

Example 3 Optimization of Solvent Level in a Low Alcohol Mouth Rinse

To optimize solvent (ethanol, sorbitol, propylene glycol) levels forlow-alcohol essential oil mouth rinse formulations, a central compositedesign was used for these three factors. Fifteen formulations wereprepared and tested using the single-species S. mutans model describedin Example 2, and log RLU was monitored to evaluate bioactivity. Sterilewater was used as the negative control.

The fifteen formulations, as well as results of the S. mutans biofilmkill tests, are shown on Tables 3A and 3B. Final formulations wereadjusted to pH 4.2 with 0.1M NaOH or 0.1M HCl if necessary. A typicalM-factor for a commercially available alcohol containing essential oilmouth rinse is about 2.1 (log RLU of 5.8) in this model.

TABLE 3A Formulations 3A 3B 3C 3D 3E 3F 3G 3H (% (% (% (% (% (% (% (%Ingredients w/w) w/w) w/w) w/w) w/w) w/w) w/w) w/w) Propylene 2.82 2.825.50 5.50 5.50 8.17 8.17 5.50 glycol Cremophor 0.1 0.1 0.1 0.1 0.1 0.10.1 0.1 (PEG Castor Oil) Ethanol 2.02 7.97 10.00 5.00 5.00 2.03 2.025.00 Benzoic Acid 0.08 0.08 0.08 0.0 0.08 0.08 0.08 0.08 Menthol 0.0420.042 0.042 0.042 0.042 0.042 0.042 0.042 Methyl 0.060 0.060 0.060 0.0600.060 0.060 0.060 0.060 salicylate Thymol 0.064 0.064 0.064 0.064 0.0640.064 0.064 0.064 Eucalyptol 0.092 0.092 0.092 0.092 0.092 0.092 0.0920.092 Sodium Lauryl 0.30 0.30 0.30 0.30 0.30 0.30 0.30 0.30 SulfateSorbitol 15.94 4.05 10.00 10.00 — 4.05 15.94 20.00 (70% solution) Sodium0.07 0.07 0.07 0.07 0.07 0.07 0.07 0.07 Benzoate Flavor 0.30 0.30 0.300.30 0.30 0.30 0.30 0.30 Saccharin 0.12 0.12 0.12 0.12 0.12 0.12 0.120.12 FD&C Green #3 0.0005 0.0005 0.0005 0.0005 0.0005 0.0005 0.00050.0005 Purified Water QS QS QS QS QS QS QS QS USP TOTAL 100.0 100.0100.0 100.0 100.0 100.0 100.0 100.0 log RLU 5.08 4.91 4.38 4.44 4.774.67 4.64 4.86 M-factor 2.82 2.99 3.52 3.46 3.13 3.23 3.26 3.04

TABLE 3B Formulations 3J 3K 3L 3N 3O Negative 3I (% (% (% 3M (% (%Control Ingredients (% w/w) w/w) w/w) w/w) (% w/w) w/w) w/w) (% w/w)Propylene 2.82 8.18 8.18 5.50 2.82 1.00 10.00 100 glycol Cremophor 0.10.1 0.1 0.1 0.1 0.1 0.1 — (PEG Castor Oil) Ethanol 2.02 7.97 7.97 — 7.975.00 5.00 — Benzoic Acid 0.08 0.08 0.08 0.08 0.08 0.08 0.08 — Menthol0.042 0.042 0.042 0.042 0.042 0.042 0.042 — Methyl 0.060 0.060 0.0600.060 0.060 0.060 0.060 — salicylate Thymol 0.064 0.064 0.064 0.0640.064 0.064 0.064 — Eucalyptol 0.092 0.092 0.092 0.092 0.092 0.092 0.092— Sodium Lauryl 0.30 0.30 0.30 0.30 0.30 0.30 0.30 — Sulfate Sorbitol(70% 4.05 4.05 15.95 10.00 15.94 10.00 10.00 — solution) Sodium 0.070.07 0.07 0.07 0.07 0.07 0.07 — Benzoate Flavor 0.30 0.30 0.30 0.30 0.300.30 0.30 — Saccharin 0.12 0.12 0.12 0.12 0.12 0.12 0.12 — FD&C Green0.0005 0.0005 0.0005 0.0005 0.0005 0.0005 0.0005 — #3 Purified Water QSQS QS QS QS QS QS — USP TOTAL 100.0 100.0 100.0 100.0 100.0 100.0 100.0— log RLU 4.56 4.67 4.45 4.58 4.91 4.70 4.62 7.9 M-factor 3.34 3.29 3.453.32 2.99 3.2 3.28 0

As illustrated in Tables 3A and 3B, at a level of 0.3%, sodium laurylsulfate and a total oil phase content of about 0.6% w/w, the propyleneglycol (or polyol solvent) concentration is optimum between 4% and 10%w/w and sorbitol (or sugar alcohol solvent) is optimum between 6% and14% w/w when added as a 70% sorbitol solution. Ethanol concentration didnot have a large impact on efficacy in this system.

Example 4 Optimization of Solvent Levels in a Non-Alcohol Mouth Rinsewith a Two-Factor Central Composite Design

To optimize solvent (sorbitol, propylene glycol) levels for non-alcoholessential oil mouth rinse formulations, a central composite design wasused for these two factors. Nine formulations were prepared and testedusing the single-species S. mutans model described in Example 2, and logRLU was monitored to evaluate bioactivity. Sterile water was used as thenegative control.

The nine formulations, as well as results of the S. mutans biofilm killtests, are shown on Table 4. Final formulations were adjusted to pH 4.2with 0.1M NaOH or 0.1M HCl if necessary. A typical M-factor for acommercially available alcohol containing essential oil mouth rinse isabout 2.1 (log RLU of 5.8) in this model.

TABLE 4 Formulations Negative 4A 4B 4C 4D 4E 4F 4G 4H 4I ControlIngredients (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (%w/w) (% w/w) (% w/w) Propylene 7.20 7.20 12.50 12.50 17.80 5.00 12.5017.80 20.00 100 glycol Menthol 0.042 0.042 0.042 0.042 0.042 0.042 0.0420.042 0.042 Methyl 0.060 0.060 0.060 0.060 0.060 0.060 0.060 0.060 0.060salicylate Thymol 0.065 0.065 0.065 0.065 0.065 0.065 0.065 0.065 0.065Eucalyptol 0.093 0.093 0.093 0.093 0.093 0.093 0.093 0.093 0.093 Flavor0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 Sorbitol 3.66 21.34 25.00 —21.34 12.50 12.50 3.66 12.50 (70% solution) Sodium 0.35 0.35 0.35 0.350.35 0.35 0.35 0.35 0.35 Lauryl Sulfate Purified QS QS QS QS QS QS QS QSQS Water USP Benzoic 0.086 0.086 0.086 0.086 0.086 0.086 0.086 0.0860.086 Acid Sodium 0.077 0.077 0.077 0.077 0.077 0.077 0.077 0.077 0.077Benzoate Saccharin 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06Sucralose 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 FD&C 0.00050.0005 0.0005 0.0005 0.0005 0.0005 0.0005 0.0005 0.0005 Green #3 TOTAL100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 log RLU 5.96 5.445.57 5.69 5.77 5.27 5.38 5.8 5.87 7.94 M-factor 1.98 2.50 2.37 2.25 2.172.67 2.56 2.14 2.07 0

As illustrated in Table 4, at a level of 0.35% w/w sodium laurylsulfate, and a total oil phase content of about 0.36% w/w, the propyleneglycol (or polyol solvent) concentration is optimum between 5 and 13%w/w while sorbitol (or sugar alcohol solvent) is optimum between 10 and25% w/w when added as a 70% sorbitol solution. Solvent optimums can varydepending on surfactant concentration and flavor choice.

Example 5 Evaluation of Other Glycol Solvents

Two formulations were prepared and tested using the single-species S.mutans model described in Example 2, with log RLU monitored to evaluatebioactivity. Sterile water was used as the negative control.

The purpose was to compare non-alcohol essential oil formulationscontaining propylene glycol to non-alcohol essential oil formulationscontaining other glycol solvents, such as 1,3-propanediol.

The formulations, as well as results of the S. mutans biofilm killtests, are shown on Table 5. Final formulations were adjusted to pH 4.2with 0.1M NaOH or 0.1M HCl if necessary. A typical M-factor for acommercially available alcohol containing essential oil mouth rinse isabout 2.1 (log RLU of 5.8) in this model.

TABLE 5 Formulations Negative 5A 5B Control Ingredients (% w/w) (% w/w)(% w/w) Purified Water USP QS QS 100 Sorbitol (70% solution) 10.00 10.00— 1,3-propanediol 7.00 — — Propylene glycol — 7.00 — Sodium laurylsulfate 0.30 0.30 — Sodium Saccharin 0.12 0.12 — Flavor 0.10 0.10 —Benzoic Acid 0.10 0.10 — Sodium Benzoate 0.05 0.05 — Eucalyptol 0.0930.093 — Thymol 0.065 0.065 — Methyl Salicylate 0.060 0.060 — Menthol0.042 0.042 — FD&C Green #3 0.0005 0.0005 — TOTAL 100.00 100.00 — logRLU 4.35 4.42 7.94 M-factor 3.59 3.52 0

The RLU values for ATP from oral biofilms treated with formulation 5A(1,3-propanediol as the polyol solvent) and formulation 5B (propyleneglycol as the polyol solvent)\ are very comparable (M-factors equaling3.59 and 3.52, respectively), indicating that propylene glycol canpotentially be substituted with other polyol solvents (i.e.,1,3-propanediol) and still retain bioactivity. A typical M-factor for acommercially available alcohol containing essential oil mouth rinse isabout 2.1 (log RLU of 5.8) in this model.

Example 6 Effect of Poloxamer

Four formulations were prepared and tested for mixed-species biofilmkill using the single species model discussed in Example 2. The negativecontrol was sterile water.

The four formulations, as well as results of the single species biofilmkill tests, are shown on Table 6. Final formulations were adjusted to pH4.2 with 0.1M NaOH or 0.1M HCl if necessary. A typical M-factor for acommercially available alcohol containing essential oil mouth rinse isabout 2.1 (log RLU of 5.8) in this model.

TABLE 6 Formulations Negative 6A 6B 6C 6D Control Ingredients (% w/w) (%w/w) (% w/w) (% w/w) (% w/w) Propylene 7.00 7.00 7.00 7.00 100 glycolMenthol 0.042 0.042 0.042 0.042 — Methyl 0.060 0.060 0.060 0.060 —salicylate Thymol 0.065 0.065 0.065 0.065 — Eucalyptol 0.093 0.093 0.0930.093 — Flavor 0.100 0.100 0.100 0.100 — Sorbitol 10.00 10.00 10.0010.00 — Sodium lauryl 0.35 0.20 0.20 0.20 — sulfate Poloxamer 407 0.000.20 0.50 0.75 — Purified Water QS QS QS QS — USP Benzoic Acid 0.0860.086 0.086 0.086 — Sodium 0.077 0.077 0.077 0.077 — Benzoate Saccharin0.060 0.060 0.060 0.060 — Sucralose 0.01 0.01 0.01 0.01 — FD&C 0.00050.0005 0.0005 0.0005 — Green #3 TOTAL 100.0 100.0 100.0 100.0 — log RLU6.25 6.60 7.20 7.52 7.94 M-factor 1.69 1.34 0.74 0.42 0

The log RLU for water was 7.94. The table shows that as the amount ofPoloxamer 407 added to the formulation was increased, the log RLUs(relative light units) increased. Increasing log RLUs indicates moreviable bacteria remaining on the substrate. So, compositions free ofPoloxamer are more effective on single species biofilm. The M-factorsfor all the formulations containing Poloxamer 407 (formulations 6B-6D)were less than 1.50.

Example 7 Evaluation of Glycerin as a Glycol Solvent

Six formulations were prepared and tested using the single-species S.mutans model described in Example 2, with log RLU monitored to evaluatebioactivity. Sterile water was used as the negative control.

The purpose was to compare non-alcohol essential oil formulationscontaining propylene glycol to non-alcohol essential oil formulationscontaining glycerin or glycerin/propylene glycol combinations.

The formulations, as well as results of the S. mutans biofilm killtests, are shown on Table 7. Final formulations were adjusted to pH 4.2with 0.1M NaOH or 0.1M HCl if necessary. A typical M-factor for acommercially available alcohol containing essential oil mouth rinse isabout 2.1 (log RLU of 5.8) in this model.

TABLE 7 Formulations Negative 7A 7B 7C 7D 7E 7F Control Ingredients (%w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) Propylene 10.0005.000 — 5.000 — — — glycol Glycerin — 5.000 10.000 10.000 20.000 5.000 —Sorbitol — — — — — 10.000 — Benzoic Acid 0.100 0.100 0.100 0.100 0.1000.100 — Menthol 0.042 0.042 0.042 0.042 0.042 0.042 — Methyl 0.060 0.0600.060 0.060 0.060 0.060 — salicylate Thymol 0.064 0.064 0.064 0.0640.064 0.064 — Eucalyptol 0.092 0.092 0.092 0.092 0.092 0.092 — Sodiumlauryl 0.350 0.350 0.350 0.350 0.350 0.350 — sulfate Sodium 0.080 0.0800.080 0.080 0.080 0.080 — Benzoate Purified Water QS QS QS QS QS QS 100USP TOTAL 100 100 100 100 100 100 — log RLU 6.20 6.65 6.30 6.32 6.466.12 7.9 M-factor 1.7 1.25 1.6 1.58 1.44 1.78 0

The log RLU values based on ATP from oral biofilms treated with bothformulations are very comparable, indicating that propylene glycol canpotentially be substituted with other glycol solvents and bioactivitywill be maintained. The log RLU values based on ATP from oral biofilmstreated with formulation 7A (propylene glycol) and formulation 7C(glycerin) are comparable (M-factors equaling 1.7 and 1.6,respectively), indicating that propylene glycol can potentially besubstituted with other polyol solvents (i.e., glycerin) and still retainbioactivity.

Example 8 Combination of SLS with Other Surfactants

Three formulations were prepared and tested for mixed-species biofilmkill using a flow-through model, as shown in Example 1. Sterile waterwas used as the negative control.

The three formulations, as well as results of the mixed-species biofilmkill tests, are shown on Table 8. Final formulations were adjusted to pH4.2 with 0.1M NaOH or 0.1M HCl if necessary. A typical M-factor for acommercially available alcohol containing essential oil mouth rinse isabout 1.8 (log RLU of 5.7) in this model.

TABLE 8 Formulations Negative 8A 8B 8C Control Ingredients (% w/w) (%w/w) (% w/w) (% w/w) Propylene glycol 7.00 0.00 0.00 — Glycerin 0.0010.00 10.00 — Menthol 0.042 0.042 0.042 — Methyl salicylate 0.060 0.0600.060 — Thymol 0.064 0.064 0.064 — Eucalyptol 0.092 0.092 0.092 — Flavor0.100 0.100 0.100 — Sorbitol 10.00 10.00 10.00 — Sodium lauryl sulfate0.35 0.15 0.00 — Sodium methyl cocoyl 0.00 0.15 0.30 — taurate PurifiedWater USP QS QS QS 100 Benzoic Acid 0.086 0.086 0.086 — Sodium Benzoate0.077 0.077 0.077 — FD&C Green #3 0.0005 0.0005 0.0005 — TOTAL 100.0100.0 100.0 — log RLU 5.47 5.18 6.29 7.5 M-factor 2.03 2.32 1.21 0

The log RLU values for ATP from oral biofilms treated with sodium laurylsulfate and sodium lauryl sulfate/sodium methyl cocoyl taurateformulations are very comparable, indicating that the sodium laurylsulfate level can be reduced when an additional surfactant (e.g, sodiummethyl cocoyl taurate) is added to the formulation (as indicated byM-factors of 2.03 and 2.32, respectively) and bioactivity will bemaintained. If no alkyl sulfate surfactant is present, a loss ofbioactivity is observed (as indicated by the lower M-factor of 1.21).

1. A reduced-alcohol antimicrobial mouth rinse composition comprising:a. an oil phase comprising one or more antimicrobial essential oils; b.a solvent system comprising: i. at least one polyol solvent and ii. atleast one sugar alcohol solvent in an amount not exceeding about 17% w/vof the composition; c. at least one alkyl sulfate surfactant; d.optionally, at least one other surfactant; and e. an aqueous phasecomprising water wherein the mouth rinse composition is a microemulsioncomprising micelles having a aggregate size less than about 200 nm andwherein the composition is free of bioavailability affecting compoundsand further wherein the composition is essentially free of C₂ to C₄monohydric alcohols.
 2. A mouth rinse according to claim 1, wherein theantimicrobial essential oils are selected from the group consisting ofmenthol, eucalyptol, methyl salicylate, thymol and mixtures thereof. 3.A mouth rinse according to claim 2, wherein the antimicrobial essentialoils are a mixture of menthol, eucalyptol, methyl salicylate and thymol.4. A mouth rinse according to claim 1, wherein the polyol solvent isselected from the group consisting of polyhydric alkanes, polyhydricalkane esters, polyalkene glycols and mixtures thereof.
 5. A mouth rinseaccording to claim 4, wherein the polyol is a polyhydric alkane.
 6. Amouth rinse according to claim 5, wherein the polyhydric alkane ispropylene glycol.
 7. A mouth rinse according to claim 1, wherein thesugar alcohol solvent is selected from as the group consisting ofxylitol, sorbitol, mannitol, maltitol, inositol, allitol, altritol,dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol,erythritol and mixtures thereof.
 8. A mouth rinse according to claim 7,wherein the sugar alcohol solvent is sorbitol.
 9. A mouth rinseaccording to claim 1, wherein the polyol solvent and the sugar alcoholsolvent are present at a ratio of from about 10:1 to about 1:10 byweight.
 10. A mouth rinse according to claim 9, wherein the polyolsolvent and the sugar alcohol solvent are present at a ratio of fromabout 5:1 to about 1:5 by weight.
 11. A mouth rinse according to claim1, wherein the alkyl sulfate surfactant is an alkyl sulfate surfactanthaving an even numbered C₈ to C₁₈ chain length.
 12. A mouth rinseaccording to claim 11, wherein the alkyl sulfate surfactant is selectedfrom the group consisting of sodium lauryl sulfate, hexadecyl sulfateand mixtures thereof.
 13. A mouth rinse according to claim 1, whereinthe ratio of the oil phase to solvent system to the alkyl sulfatesurfactant in the composition is about 1:60:1.5 by weight.
 14. A mouthrinse according to claim 13, wherein the ratio of the oil phase to thesolvent system to the alkyl sulfate surfactant in the composition isabout 1:200:1.5 by weight.
 15. A mouthrinse according to claim 1,wherein the bioavailability affecting compounds are selected from thegroup consisting of polyethylene oxide/polypropylene oxide blockcopolymers such as poloxamers, cyclodextrins, polysorbate and mixtures.16. A mouthrinse according to claim 1, wherein the composition is freeof bioavailability affecting compounds.
 17. A mouthrinse according toclaim 1, wherein the composition is free of C₂-C₄ monohydric alcohols.18. A mouthrinse according to claim 1, wherein the composition has anM-factor greater than about 0.5.
 19. A mouthrinse according to claim 16,wherein the composition has an M-factor greater than about 1.0.
 20. Amouthrinse according to claim 17, wherein the composition has anM-factor greater than about 2.0.